tbuckley/cabot-search huggingface dataset:
Double-Modal Locomotion of a Hydrogel Ultra-Soft Magnetic Miniature Robot with Switchable Forms
Authors: Shihao Zhong, Zhengyuan Xin, Yaozhen Hou, Yang Li, Hen-Wei Huang, Tao Sun, Qing Shi, Huaping Wang
Journal: Cyborg and Bionic Systems (2023)

Flexible miniature robots are expected to enter difficult-to-reach areas in vivo to carry out targeted operations, attracting widespread attention. However, it is challenging for the existing soft miniature robots to substantially alter their stable shape once the structure is designed. This limitation leads to a fixed motion mode, which subsequently restricts their operating environment. In this study, we designed a biocompatible flexible miniature robot with a variable stable form that is capable of adapting to complex terrain environments through multiple movement modes. Inspired by the reversible stretching reaction of alginate saline gel stimulated by changes in environmental ion concentration, we manufactured a morphologically changeable super-soft hydrogel miniature robot body. According to the stretch and contraction shapes of the flexible hydrogel miniature robot, we designed magnetic fields for swing and rolling motion modes to realize multi-shape movement. The experimental results demonstrate that the deflection angle of the designed flexible miniature robot is reversible and can reach a maximum of 180°. The flexible miniature robot can complete forward swinging in the bar stretch state and tumbling motion in the spherical state. We anticipate that flexible hydrogel miniature robots with multiple morphologies and multimodal motion have great potential for biomedical applications in complex, unstructured, and enclosed living environments.
Inhibition of intestinal FXR activity as a possible mechanism for the beneficial effects of a probiotic mix supplementation on lipid metabolism alterations and weight gain in mice fed a high fat diet
Authors: Alice Beau, Bérengère Benoit, Mélanie Le Barz, Emmanuelle Meugnier, Armelle Penhoat, Catherine Calzada, Claudie Pinteur, Emmanuelle Loizon, Stéphanie Chanon, Aurélie Vieille-Marchiset, Valérie Sauvinet, Murielle Godet, Fabienne Laugerette, Sophie Holowacz, Elsa Jacouton, Marie-Caroline Michalski, Hubert Vidal
Journal: Gut Microbes (2023)

Supplementation with probiotics has emerged as a promising therapeutic tool to manage metabolic diseases. We investigated the effects of a mix of Bifidobacterium animalis subsp. lactis LA804 and Lactobacillus gasseri LA806 on high-fat (HF) diet -induced metabolic disease in mice. Supplementation with the probiotic mix in HF diet-fed mice (HF-Pr2) reduced weight and fat mass gains, decreased hepatic lipid accumulation, and lowered plasma triglyceride peak during an oral lipid tolerance test. At the molecular level, the probiotic mix protected against HF-induced rise in mRNA levels of genes related to lipid uptake, metabolism, and storage in the liver and white adipose tissues, and strongly decreased mRNA levels of genes related to inflammation in the white adipose tissue and to oxidative stress in the liver. Regarding intestinal homeostasis, the probiotic mix did not prevent HF-induced gut permeability but slightly modified microbiota composition without correcting the dysbiosis induced by the HF diet. Probiotic supplementation also modified the cecal bile acid (BA) profile, leading to an increase in the Farnesoid-X-Receptor (FXR) antagonist/agonist ratio between BA species. In agreement, HF-Pr2 mice exhibited a strong inhibition of FXR signaling pathway in the ileum, which was associated with lipid metabolism protection. This is consistent with recent reports proposing that inhibition of intestinal FXR activity could be a potent mechanism to overcome metabolic disorders. Altogether, our results demonstrate that the probiotic mix evaluated, when administered preventively to HF diet-fed mice could limit obesity and associated lipid metabolism disorders, likely through the inhibition of FXR signaling in the intestinal tract.
Pharmacomicrobiomics of cell-cycle specific anti-cancer drugs – is it a new perspective for personalized treatment of cancer patients?
Authors: Karolina Kaźmierczak-Siedlecka, Nikola Bulman, Paweł Ulasiński, Bartosz Kamil Sobocki, Karol Połom, Luigi Marano, Leszek Kalinowski, Karolina Skonieczna-Żydecka
Journal: Gut Microbes (2023)

Intestinal bacteria are equipped with an enzyme apparatus that is involved in the active biotransformation of xenobiotics, including drugs. Pharmacomicrobiomics, a new area of pharmacology, analyses interactions between bacteria and xenobiotics. However, there is another side to the coin. Pharmacotherapeutic agents can significantly modify the microbiota, which consequently affects their efficacy. In this review, we comprehensively gathered scientific evidence on the interplay between anticancer therapies and gut microbes. We also underlined how such interactions might impact the host response to a given therapy. We discuss the possibility of modulating the gut microbiota to increase the effectiveness/decrease the incidence of adverse events during tumor therapy. The anticipation of the future brings new evidence that gut microbiota is a target of interest to increase the efficacy of therapy.
Hybrid Endometrial‐Derived Hydrogels: Human Organoid Culture Models and In Vivo Perspectives
Authors: María Gómez‐Álvarez, Clara Bueno‐Fernandez, Adolfo Rodríguez‐Eguren, Emilio Francés‐Herrero, Marcos Agustina‐Hernández, Amparo Faus, Fernando Gisbert Roca, Cristina Martínez‐Ramos, Amparo Galán, Antonio Pellicer, Hortensia Ferrero, Irene Cervelló
Journal: Advanced Healthcare Materials (2023)

Abstract The endometrium plays a vital role in fertility, providing a receptive environment for embryo implantation and development. Understanding the endometrial physiology is essential for developing new strategies to improve reproductive healthcare. Human endometrial organoids (hEOs) are emerging as powerful models for translational research and personalized medicine. However, most hEOs are cultured in a 3D microenvironment that significantly differs from the human endometrium, limiting their applicability in bioengineering. This study presents a hybrid endometrial‐derived hydrogel that combines the rigidity of PuraMatrix (PM) with the natural scaffold components and interactions of a porcine decellularized endometrial extracellular matrix (EndoECM) hydrogel. This hydrogel provides outstanding support for hEO culture, enhances hEO differentiation efficiency due to its biochemical similarity with the native tissue, exhibits superior in vivo stability, and demonstrates xenogeneic biocompatibility in mice over a 2‐week period. Taken together, these attributes position this hybrid endometrial‐derived hydrogel as a promising biomaterial for regenerative treatments in reproductive medicine.
Emerging Technologies in Cardiac Pacing
Authors: Ramya Vajapey, Mina K. Chung
Journal: Annual Review of Medicine (2023)

Cardiac pacing to treat bradyarrhythmias has evolved in recent decades. Recognition that a substantial proportion of pacemaker-dependent patients can develop heart failure due to electrical and mechanical dyssynchrony from traditional right ventricular apical pacing has led to development of more physiologic pacing methods that better mimic normal cardiac conduction and provide synchronized ventricular contraction. Conventional biventricular pacing has been shown to benefit patients with heart failure and conduction system disease but can be limited by scarring and fibrosis. His bundle pacing and left bundle branch area pacing are novel techniques that can provide more physiologic ventricular activation as an alternative to conventional or biventricular pacing. Leadless pacing has emerged as another alternative pacing technique to overcome limitations in conventional transvenous pacemaker systems. Our objective is to review the evolution of cardiac pacing and explore these new advances in pacing strategies. Expected final online publication date for the Annual Review of Medicine, Volume 75 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
The Scorpionfly (<i>Panorpa cognata</i>) Genome Highlights Conserved and Derived Features of the Peculiar Dipteran X Chromosome
Authors: Clementine Lasne, Marwan Elkrewi, Melissa A Toups, Lorena Layana, Ariana Macon, Beatriz Vicoso
Journal: Molecular Biology and Evolution (2023)

Abstract Many insects carry an ancient X chromosome—the Drosophila Muller element F—that likely predates their origin. Interestingly, the X has undergone turnover in multiple fly species (Diptera) after being conserved for more than 450 My. The long evolutionary distance between Diptera and other sequenced insect clades makes it difficult to infer what could have contributed to this sudden increase in rate of turnover. Here, we produce the first genome and transcriptome of a long overlooked sister-order to Diptera: Mecoptera. We compare the scorpionfly Panorpa cognata X-chromosome gene content, expression, and structure to that of several dipteran species as well as more distantly related insect orders (Orthoptera and Blattodea). We find high conservation of gene content between the mecopteran X and the dipteran Muller F element, as well as several shared biological features, such as the presence of dosage compensation and a low amount of genetic diversity, consistent with a low recombination rate. However, the 2 homologous X chromosomes differ strikingly in their size and number of genes they carry. Our results therefore support a common ancestry of the mecopteran and ancestral dipteran X chromosomes, and suggest that Muller element F shrank in size and gene content after the split of Diptera and Mecoptera, which may have contributed to its turnover in dipteran insects.
Injectable Microporous Annealed Crescent‐Shaped (MAC) Particle Hydrogel Scaffold for Enhanced Cell Infiltration
Authors: Rui‐Chian Tang, Lily Shang, Philip O. Scumpia, Dino Di Carlo
Journal: Advanced Healthcare Materials (2023)

Hydrogels are widely used for tissue engineering applications to support cellular growth, yet the tightly woven structure often restricts cell infiltration and expansion. Consequently, granular hydrogels with microporous architectures have emerged as a new class of biomaterial. Particularly, the development of microporous annealed particle (MAP) hydrogel scaffolds has shown improved stability and integration with host tissue. However, the predominant use of spherically shaped particles limits scaffold porosity, potentially limiting the level of cell infiltration. Here, a novel microporous annealed crescent-shaped particle (MAC) scaffold that is predicted to have improved porosity and pore interconnectivity in silico is presented. With microfluidic fabrication, tunable cavity sizes that optimize interstitial void space features are achieved. In vitro, cells incorporated into MAC scaffolds form extensive 3D multicellular networks. In vivo, the injectable MAC scaffold significantly enhances cell infiltration compared to spherical MAP scaffolds, resulting in increased numbers of myofibroblasts and leukocytes present within the gel without relying on external biomolecular chemoattractants. The results shed light on the critical role of particle shape in cell recruitment, laying the foundation for MAC scaffolds as a next-generation granular hydrogel for diverse tissue engineering applications.
Therapeutic Drug Monitoring: A Tool to Optimize Treatment of Inflammatory Joint Diseases
Authors: Silje W. Syversen, Johanna E. Gehin, Guro L. Goll, Nils Bolstad, Espen A. Haavardsholm, Siri Lillegraven
Journal: Arthritis & Rheumatology (2023)

Disclosure Form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The pathogenesis and potential therapeutic targets in sepsis
Authors: Wendan Zhang, Honghong Jiang, Gaosong Wu, Pengli Huang, Haonan Wang, Huazhang An, Sanhong Liu, Weidong Zhang
Journal: MedComm (2023)

Sepsis is defined as "a life-threatening organ dysfunction caused by dysregulated host systemic inflammatory and immune response to infection." At present, sepsis continues to pose a grave healthcare concern worldwide. Despite the use of supportive measures in treating traditional sepsis, such as intravenous fluids, vasoactive substances, and oxygen plus antibiotics to eradicate harmful pathogens, there is an ongoing increase in both the morbidity and mortality associated with sepsis during clinical interventions. Therefore, it is urgent to design specific pharmacologic agents for the treatment of sepsis and convert them into a novel targeted treatment strategy. Herein, we provide an overview of the molecular mechanisms that may be involved in sepsis, such as the inflammatory response, immune dysfunction, complement deactivation, mitochondrial damage, and endoplasmic reticulum stress. Additionally, we highlight important targets involved in sepsis-related regulatory mechanisms, including GSDMD, HMGB1, STING, and SQSTM1, among others. We summarize the latest advancements in potential therapeutic drugs that specifically target these signaling pathways and paramount targets, covering both preclinical studies and clinical trials. In addition, this review provides a detailed description of the crosstalk and function between signaling pathways and vital targets, which provides more opportunities for the clinical development of new treatments for sepsis.
Leucine‐rich repeat kinase 2 (LRRK2) inhibition upregulates microtubule‐associated protein 1B to ameliorate lysosomal dysfunction and parkinsonism
Authors: Kang Chen, Fei Tang, Bin Du, Zhe‐Zhou Yue, Ling‐Ling Jiao, Xu‐Long Ding, Qing‐Zhang Tuo, Jie Meng, Si‐Yu He, Lunzhi Dai, Peng Lei, Xia‐Wei Wei
Journal: MedComm (2023)

Mutations in
Single‐cell transcriptomic atlas of distinct early immune responses induced by SARS‐CoV‐2 Proto or its variants in rhesus monkey
Authors: Yun Yang, Tingfu Du, Wenhai Yu, Yanan Zhou, Chengyun Yang, Dexuan Kuang, Junbin Wang, Cong Tang, Haixuan Wang, Yuan Zhao, Hao Yang, Qing Huang, Daoju Wu, Bai Li, Qiangming Sun, Hongqi Liu, Shuaiyao Lu, Xiaozhong Peng
Journal: MedComm (2023)

Immune responses induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection play a critical role in the pathogenesis and outcome of coronavirus disease 2019 (COVID-19). However, the dynamic profile of immune responses postinfection by SARS-CoV-2 variants of concern (VOC) is not fully understood. In this study, peripheral blood mononuclear cells single-cell sequencing was performed to determine dynamic profiles of immune response to Prototype, Alpha, Beta, and Delta in a rhesus monkey model. Overall, all strains induced dramatic changes in both cellular subpopulations and gene expression levels at 1 day postinfection (dpi), which associated function including adaptive immune response, innate immunity, and IFN response. COVID-19-related genes revealed different gene profiles at 1 dpi among the four SARS-CoV-2 strains, including genes reported in COVID-19 patients with increased risk of autoimmune disease and rheumatic diseases. Delta-infected animal showed inhibition of translation pathway. B cells, T cells, and monocytes showed much commonality rather than specificity among the four strains. Monocytes were the major responders to SARS-CoV-2 infection, and the response lasted longer in Alpha than the other strains. Thus, this study reveals the early immune responses induced by SARS-CoV-2 Proto or its variants in nonhuman primates, which is important information for controlling rapidly evolving viruses.
Decellularized diseased tissues: current state‐of‐the‐art and future directions
Authors: Xiang Li, Jianyang Shan, Xin Chen, Haomin Cui, Gen Wen, Yaling Yu
Journal: MedComm (2023)

Decellularized matrices derived from diseased tissues/organs have evolved in the most recent years, providing novel research perspectives for understanding disease occurrence and progression and providing accurate pseudo models for developing new disease treatments. Although decellularized matrix maintaining the native composition, ultrastructure, and biomechanical characteristics of extracellular matrix (ECM), alongside intact and perfusable vascular compartments, facilitates the construction of bioengineered organ explants in vitro and promotes angiogenesis and tissue/organ regeneration in vivo, the availability of healthy tissues and organs for the preparation of decellularized ECM materials is limited. In this paper, we review the research advancements in decellularized diseased matrices. Considering that current research focuses on the matrices derived from cancers and fibrotic organs (mainly fibrotic kidney, lungs, and liver), the pathological characterizations and the applications of these diseased matrices are mainly discussed. Additionally, a contrastive analysis between the decellularized diseased matrices and decellularized healthy matrices, along with the development in vitro 3D models, is discussed in this paper. And last, we have provided the challenges and future directions in this review. Deep and comprehensive research on decellularized diseased tissues and organs will promote in-depth exploration of source materials in tissue engineering field, thus providing new ideas for clinical transformation.
Clinical Images: Hairy kidney in <scp>IgG4</scp>‐related disease
Authors: Tomoyuki Mutoh, Ryoto Sasaki, Kazuhiro Sakamoto, Masataka Kudo
Journal: Arthritis & Rheumatology (2023)

Disclosure form Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Glucagon‐like peptide‐1 receptor agonist regulates fat browning by altering the gut microbiota and ceramide metabolism
Authors: Ke Lin, Chunyan Dong, Binyan Zhao, Bailing Zhou, Li Yang
Journal: MedComm (2023)

Abstract Studies have shown that antidiabetic drugs can alter the gut microbiota. The hypoglycemic effects of the drugs can be attributed in part to certain species in the gut microbiome that help the drugs work more effectively. In addition, increasing energy expenditure via the induction of adipose tissue browning has become an appealing strategy to treat obesity and associated metabolic complications. Currently, glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA) treatment for metabolic disorders such as obesity and type 2 diabetes has been widely studied. To determine the mechanism of a long‐acting GLP‐1 RA affects adipose tissue browning and the gut microbiome, we treated high‐fat diet mice with GLP‐1 RA and demonstrated that the drug can regulate adipose tissue browning. 16S rRNA and untargeted metabolomics assays suggested that it increased the abundance of bacterium Lactobacillus reuteri and decreased serum ceramide levels in mice. L. reuteri was negatively correlated with ceramide. We found that the mechanism of ceramide decline was alkaline ceramidase 2 (Acer2) overexpression. Moreover, L. reuteri can play a therapeutic synergistic role with GLP‐1 RA, suggesting that gut microbiota can be used as a part of the treatment of diabetes.
Neuroimmunology of the Lung
Authors: Rossana Azzoni, Olaf Perdijk, Nicola L. Harris, Benjamin J. Marsland
Journal: Annual Review of Immunology (2023)

Barrier tissues are highly innervated by sensory and autonomic nerves that are positioned in close proximity to both stromal and immune cell populations. Together with a growing awareness of the far-reaching consequences of neuroimmune interactions, recent studies have uncovered key mechanisms through which they contribute to organ homeostasis and immunity. It has also become clear that dysregulation of such interactions is implicated in the development of chronic lung diseases. This review describes the characteristics of the lung nervous system and discusses the molecular mechanisms that underlie lung neuroimmune interactions in infection and disease. We have contextualized the current literature and identified opportune areas for further investigation. Indeed, both the lung-brain axis and local neuroimmune interactions hold enormous potential for the exploration and development of novel therapeutic strategies targeting lung diseases.
Pyroptosis Induction with Nanosonosensitizer‐Augmented Sonodynamic Therapy Combined with PD‐L1 Blockade Boosts Efficacy against Liver Cancer
Authors: Nisi Zhang, Wenlong Zeng, Yunxue Xu, Rui Li, Mengxuan Wang, Yijia Liu, Shuai Qu, Katherine W. Ferrara, Zhifei Dai
Journal: Advanced Healthcare Materials (2023)

Induction of pyroptosis can promote anti-PD-L1 therapeutic efficacy due to the release of pro-inflammatory cytokines, but current approaches can cause off target toxicity. Herein, a phthalocyanine-conjugated mesoporous silicate nanoparticle (PMSN) is designed for amplifying sonodynamic therapy (SDT) to augment oxidative stress and induce robust pyroptosis in tumors. The sub-10 nm diameter structure and c(RGDyC)-PEGylated modification enhance tumor targeting and renal clearance. The unique porous architecture of PMSN doubles ROS yield and enhances pyroptotic cell populations in tumors (25.0%) via a cavitation effect. PMSN-mediated SDT treatment efficiently reduces tumor mass and suppressed residual tumors in treated and distant sites by synergizing with PD-L1 blockade (85.93% and 77.09%, respectively). Furthermore, loading the chemotherapeutic, doxorubicin, into PMSN intensifies SDT-pyroptotic effects and increased efficacy. This is the first report of the use of SDT regimens to induce pyroptosis in liver cancer. This noninvasive and effective strategy has potential for clinical translation.
Clinical and molecular effects of oral <scp>CCR4</scp> antagonist <scp>RPT193</scp> in atopic dermatitis: A Phase 1 study
Authors: Robert Bissonnette, Janet DuBois, Paola Facheris, Ester Del Duca, Madeline Kim, Joel Correa Da Rosa, Damian L. Trujillo, Swaroop Bose, Angel D. Pagan, David Wustrow, Dirk G. Brockstedt, Brian Wong, Paul D. Kassner, Jasmina Jankicevic, William Ho, Laurence E. Cheng, Emma Guttman‐Yassky
Journal: Allergy (2023)

Abstract Background RPT193 is an orally administered small molecule antagonist of the human C‐C motif chemokine receptor 4 (CCR4) that inhibits the migration and downstream activation of T‐helper Type 2 (Th2) cells. We investigated single‐ and multiple‐ascending doses of RPT193 in healthy subjects, and multiple doses of RPT193 in subjects with moderate‐to‐severe atopic dermatitis (AD). Methods This was a first‐in‐human randomized, placebo‐controlled Phase 1a/1b monotherapy study (NCT04271514) to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and CCR4 surface receptor occupancy in eligible healthy subjects and subjects with moderate‐to‐severe AD. Clinical efficacy and skin biomarker effects of RPT193 monotherapy were assessed as exploratory endpoints in AD subjects. Results In healthy ( n = 72) and AD subjects ( n = 31), once‐daily RPT193 treatment was generally well tolerated, with no serious adverse events reported and all treatment‐emergent adverse events reported as mild/moderate. In AD subjects, numerically greater improvements in clinical efficacy endpoints were observed with RPT193 monotherapy versus placebo up to the end of the treatment period (Day 29), with statistically significant improvement, compared to Day 29 and placebo, observed 2 weeks after the end of treatment (Day 43) on several endpoints ( p &lt; .05). Moreover, significant changes in the transcriptional profile were seen in skin biopsies of RPT193‐treated versus placebo‐treated subjects at Day 29, which were also significantly correlated with improvements in clinical efficacy measures. Conclusions To our knowledge, this is the first clinical study with an oral CCR4 antagonist that showed clinical improvement coupled with modulation of the cutaneous transcriptomic profile in an inflammatory skin disease.